Guest blogger Alan Trounson — April’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

This month’s report includes an important review of studies using bone marrow stem cells for heart disease that showed some disturbingly sloppy handling of the data. It will be critical for the field to address this issue, particularly given the highly variable and often inclusive results of those studies.

But, since this is my last post as President of CIRM, I want it to address some good news in April’s stem cell literature. Two teams reported replicating the breakthrough success of Oregon’s Shoukhrat Mitalipov in creating human embryonic stem cell lines through somatic cell nuclear transfer (SCNT), also known as therapeutic cloning. Replication of results remains a cornerstone of science and it is reassuring to see two teams independently replicate the results of the Oregon team in less than a year.

SCNT, which requires placing the nucleus of a mature cell into an egg that has had its own nucleus removed, has been relatively easy to accomplish in lower mammals but impossible in humans until the Oregon success. But that work got the donor nucleus from fetal tissue or a recently born baby, so it left open the question of whether the procedure would work with a less malleable cell from an older adult.

One of the teams that repeated the work, based in Korea, created two stem cell lines, one from a 35-year-old and one from a 75-year-old. They used largely the same procedure as the Oregon team but made one key change in the protocol. Instead of waiting just 30 minutes to stimulate the egg to divide after fusing the donor nucleus and the egg, they waited two hours. They speculated that this longer incubation may have helped reprogram the genes of the older cells to behave like younger ones.

The second team, at the New York Stem Cell Foundation used a somewhat different procedure to create embryonic stem cell lines including one from the skin of a 32-year-old with diabetes. That became the first disease-specific cloned stem cell line. They modified a procedure they used to create a variant of SCNT-derived stem cells in 2011. At that time they had hypothesized that there must be something in the human egg genes that is necessary to reprogram the adult nucleus. So they left in one set of the egg genes, which resulted in stem cells that were triploid; they had two sets of genes from the donor nucleus and one from the egg. Those cell lines provided a tool for some interesting research but were never really an option for therapeutic cloning where the goal is to create stem cell that match the genetics of the donor to create repair tissue that will not be rejected by the immune system. This time they changed the way they activated the egg and modified some other steps and were able to get true SCNT stem cell lines.

Both these protocols required too many eggs to be viable for patient care procedures until they are greatly refined. However, both teams have announced that they have created iPS type stem cells from the same patients so that researchers can begin the much-needed comparison of embryonic and iPS cells.

My full report is available online, along with links to my reports from previous months.

A.T.

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